Antibacterial activity of eight Brazilian annonaceae plants

Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X. amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A. cherimolia. Amongst the investigated extracts, six showed antibacterial activity against at least one of the tested organisms at the concentration of 100 microg/mL. The most active extracts were those prepared from X. frutescens, X. amazonica, and A. ambotay. A phytochemical screening showed the presence of anonaceus acetogenins in some active extracts. Eleven diterpenoids were also tested for comparison purposes. Six were natural products, previously isolated from Xylopia sp. (kaurenoic, frutoic, xylopic, 15beta-hydroxy-kaurenoic and trachylobanic acids plus kaurenol) and five were derivatives of such compounds, obtained by esterification or reduction reactions. Trachylobanic acid showed antibacterial activity against B. subtilis and S. aureus.     

Antimalarial activity of sesquiterpene lactones from Vernonia cinerea

Two new sesquiterpene lactones, vernolides C and D as well as six known ones were isolated from the dichloromethane fraction of an aqueous extract from Vernonia cinerea. Their structures were elucidated by spectroscopic methods. Among the known sesquiterpene lactones, three of them were described in this plant for the first time. In vitro antiplasmodial evaluation showed that the three major compounds 1, 7 and 8 were active against chloroquine resistant Plasmodium falciparum strain (W2) with IC(50) 3.9, 3.7 and 3.5 microM, respectively.     

An Overview of the Chemical Characteristics,Bioactivity and Achievements Regarding the Therapeutic Usage of Acetogenins from Annona cherimola Mill.

Annona cherimola Mill., or the custard apple, is one of the species belonging to the Annonaceae family, is widely used in traditional medicine, and has been reported to be a valuable source of bioactive compounds. A unique class of secondary metabolites derived from this family are Annonaceous acetogenins, lipophilic polyketides considered to be amongst the most potent antitumor compounds. This review provides an overview of the chemical diversity, isolation procedures, bioactivity, modes of application and synthetic derivatives of acetogenins from A. cherimola Mill.     

Acetogenins in Annona muricata L. (annonaceae) leaves are potent molluscicides

An ethanolic extract of the leaves of Annona muricata was shown to be toxic to adult forms of the snail Biomphalaria glabrata (LC50 9.32 microg mL(-1)) and to larvae of the brine shrimp Artemia salina (LC50 0.49 microg mL(-1)). Activity-guided fractionation of the extract gave rise to a sample with high molluscicidal activity that contained the acetogenins, annonacin (90%), isoannonacin (6%) and goniothalamicin (4%).     

Novel Annonaceous acetogenins from Graviola (Annona muricata) fruits with strong anti-proliferative activity

Five bioactive Annonaceous acetogenins, including three new compounds, annonamuricins A (1), B (2), and C (3), one registered but no spectral data reported compounds, annonamuricin D (4), and one known compound annonacin (5) were isolated from Graviola fruit (Annona muricata) and further determined through bioassay-guided fractionation. All five compounds are C35 Anonnonaceous acetogenins with a mono-tetrahydrofuran ring and four hydroxyls. Their structures were elucidated using spectral methods as well as chemical modification after isolation via chromatographic techniques and HPLC purification. These acetogenins demonstrated potent anti-proliferative activities against human prostate cancer PC-3 cells.     

Using chemical probes to investigate the sub-inhibitory effects of azithromycin

The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.     

绿脓杆菌Pseudomonas aeruginosa BTE-1直接电催化特征

本文研究厌氧条件下产电绿脓杆菌P. aeruginosa BTE-1的电化学催化特征。研究结果表明,P. aeruginosa BTE-1菌株在厌氧条件下,不能分泌可充当电子介体的绿脓菌素,但可通过在电极表面形成生物膜呈现了直接电催化性能。P. aeruginosa BTE-1在电极表面形成生物膜与其在特定电极电位下向电极传递电子的过程直接相关,适宜的电位为+0.2 V (vs. SCE),电位过高可能会损害P. aeruginosa BTE-1细胞。室温范围内升高温度可增强P. aeruginosa BTE-1生物膜电催化活性,但过高的温度(>60℃)会抑制生物膜电催化活性。循环伏安曲线显示,在厌氧条件下形成的P. aeruginosa BTE-1生物膜,具有与典型产电菌株G. sulfurreducens相近的氧化还原电位(-0.4 V~ -0.2 V vs. SCE)。P. aeruginosa BTE-1生物膜可电催化酵母抽取物和葡萄糖,但不能电催化醋酸盐。     

阿蒂莫耶化学成分的研究及阿蒂莫耶素B的分离和结构

从阿蒂莫耶(Annona atemoya Hort)种子中, 首次分离到四个白色蜡状固体,经光谱分析, 分别为新的番荔枝内酯(Annonaceous acetogenin)-阿蒂莫耶素B(Atemoyacin B)和三个已知的番荔枝内酯Bullatacin, Molvizarin和Rollinicin。     

Promysalin, a salicylate-containing Pseudomonas putida antibiotic, promotes surface colonization and selectively targets other Pseudomonas

Under control of the Gac regulatory system, Pseudomonas putida RW10S1 produces promysalin to promote its own swarming and biofilm formation, and to selectively inhibit many other pseudomonads, including the opportunistic pathogen Pseudomonas aeruginosa. This amphipathic antibiotic is composed of salicylic acid and 2,8-dihydroxymyristamide bridged by a unique 2-pyrroline-5-carboxyl moiety. In addition to enzymes for salicylic acid synthesis and activation, the biosynthetic gene cluster encodes divergent type II fatty acid biosynthesis components, unusual fatty acid-tailoring enzymes (two Rieske-type oxygenases and an amidotransferase), an enzyme resembling a proline-loading module of nonribosomal peptide synthetases, and the first prokaryotic member of the BAHD family of plant acyltransferases. Identification of biosynthetic intermediates enabled to propose a pathway for synthesis of this bacterial colonization factor.     

Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides

Complete (1)H and (13)C NMR signal assignments of two lactucin-type sesquiterpene lactone glycosides, derivatives of 11β,13-dihydrolactucin, isolated from roots of Picris conyzoides, were achieved by one- and two-dimensional NMR experiments, allowing the correction of previously published data for cichorioside B and the structure elucidation of its new ester with 3-hydroxy-2-methylpropanoic acid. In addition, seven known sesquiterpene lactones and three phenolic compounds were isolated from the plant material.     

Two novel sesquiterpene lactones,cytotoxic vernolide-A and -B,from Vernonia cinerea

Bioassay-directed fractionation of an ethanolic extract of stems of Vernonia cinerea has resulted in the isolation of two novel sesquiterpene lactones, vernolide-A and -B. Their structures were elucidated on the basis of spectroscopic analysis. Biological evaluation showed that vernolide-A demonstrated potent cytotoxicity against human KB, DLD-1, NCI-661, and Hela tumor cell lines (ED(50)=0.02, 0.05, 0.53, 0.04 microg/ml for KB, DLD-1, NCI-661, and Hela, respectively); vernolide-B had marginal cytoxicity (ED(50)=3.78, 5.88, 6.42 microg/ml for KB, NCI-661, and Hela, respectively).     

Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.     

Cytotoxic effect of eudesmanolides isolated from flowers of Tanacetum vulgare ssp. siculum

A phytochemical analysis of the dichloromethane extract from the flowers of a subspecies of Tanacetum vulgare growing in Sicily was carried out. Five known sesquiterpene lactones with the eudesmane skeleton have been isolated and the cytotoxic activity of these compounds was tested in vitro on A549 (human lung carcinoma epithelial-like) and V79379A (Chinese hamster lung fibroblast-like) cells using the tetrazolium salt reduction (MTT) assay. All of tested compounds induced high time- and concentration-dependent cytotoxic effects.     

Synthesis of indole-based oxadiazoles and their interaction with bacterial peptidoglycan and SARS-CoV-2 main protease: In vitro,molecular docking and in silico ADME/Tox study

In the present study, Indole-based-oxadiazole (1A-17A) compounds were successfully synthesized. The structures of all synthesized compounds were fully characterized by different sophisticated spectroscopic techniques such 1H NMR, 13C NMR, and HREI-MS. Further, the synthesized compounds were explored to investigate their broad-spectrum antibacterial and antibiofilm potential against multidrug resistant Pseudomonas aeruginosa (MDR-PA) and methicillin resistant Staphylococcus aureus (MRSA). The compounds possessed a broad spectrum of antibacterial activity having MIC values of values 1–8 mg/ml against the tested microorganisms. Compound A6 and A7 shows maximum antibacterial activity against MDR-PA, whereas A6, A7 and A11 shows highest activity against MRSA. Furthermore, antibiofilm assay shows that A6, A7 and A11 showed maximum inhibition of biofilm formation and it was found that at 4 mg/ml; A6, A7 and A11 inhibit MRSA biofilm formation by 81.1, 77.5 and 75.9%, respectively; whereas in case of P. aeruginosa; A6 and A7 showed maximum biofilm inhibition and inhibit biofilm formation by 81.5 and 73.7%, respectively. Molecular docking study showed that compounds A6, A7, A8, A10, and A11 had high binding affinity to bacterial peptidoglycan, indicating their potential inhibitory activity against tested bacteria, whereas A6 and A11 were found to be the most effective inhibitors of SARS CoV-2 main protease (3CLpro), with a binding affinity of ? 7.78 kcal/mol. Furthermore, SwissADME and pkCSM-pharmacokinetics online tools was applied to calculate the ADME/Tox profile of the synthesized compounds and the toxicity of these chemicals was found to be low. The Lipinski, Veber, Ghose, and Consensus LogP criteria were also used to predict drug-likeness levels of the compounds. Our findings imply that the synthesized compounds could be a useful for the preventing and treating biofilm-related microbial infection as well as SARS-CoV2 infections.     

Cytotoxic and NF-κB inhibitory sesquiterpene lactones from Piptocoma rufescens

Six new (1-6) and eight known germacranolide-type sesquiterpene lactones, along with several known phenylpropanol coumarates and methylated flavonoids, were isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. The new compounds were identified by analysis of their spectroscopic data, with the molecular structure of 3 being established by single-crystal X-ray diffraction. The absolute configurations of the sesquiterpene lactones isolated were determined from their CD and NOESY NMR spectra, together with the analysis of Mosher ester reactions. Bioassay screening results showed the majority of the sesquiterpene lactones isolated (1-13) to be highly cytotoxic toward the HT-29 human colon cancer cell line, with the most potent compound being 15-deoxygoyazensolide (10, IC(50), 0.26 μM). In addition, several of the sesquiterpene lactones exhibited NF-κB (p65) inhibitory activity.     

Synthesis and biological activity of isoalantolactone—tryptamine conjugates

Previously unknown adducts of substituted tryptamines with sesquiterpene lactones, viz., isoalantolactone and its epoxy derivative, were synthesized by the Michael reaction. The compounds obtained were tested for various types of biological activity.     

New Acetogenins from the Seeds of Annona coriacea

From the hexane and MeOH extracts of Annona coriacea Mart . (Annonaceae) seeds, two novel acetogenins, coriapentocins A and B ( 1 and 2 , resp.) were isolated. The known acetogenin bullacin ( 3 ) was also isolated from the hexane extract. The structures of compounds 1 – 3 were elucidated by NMR and MS analysis, and relative configurations were established by comparison with literature data.     

Supercritical fluid extraction of cynaropicrin and 20-hydroxyecdysone from Leuzea carthamoides DC

Leuzea carthamoides is an adaptogenic plant containing biologically active compounds as ecdysteroids and guaianolide-type sesquiterpene lactones, conventionally extracted from the plant with ethanol. It may be a potential source of the mentioned natural compounds. Ethanol-modified near-critical CO(2) was used as selective solvent with the aim to increase the level of 20-hydroxyecdysone in the extract from L. carthamoides roots and to remove selectively cynaropicrin, a sesquiterpene lactone of bitter taste, from the leaves. The extraction conditions were varied (pressure 20-28 MPa, temperature 40-60 degrees C, ethanol concentration in the solvent 0-7.1%) and the extraction yield and extract composition were compared with the results of ethanolic extraction. The supercritical fluid extraction (SFE) from finely powdered plant was controlled by phase equilibrium. Cynaropicrin was quantitatively removed from the leaves where 89% of 20-hydroxyecdysone was retained. The extraction yield of 20-hydroxyecdysone from roots with ethanol-modified CO(2 )was lower by 30% than with ethanol but its concentration in the extract was higher by 67%.     

Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones

The sesquiterpene lactones cover a diverse and pharmacologically important diversity space. In particular, the electrophilic α-exo-methylene-γ-butyrolactone moiety that is preponderant in this natural product family has been shown to readily engage in covalent inhibition via conjugate addition of cysteine residues in target proteins. However, the synthetic accessibility of sesquiterpenes or related probes to investigate their mode of action remains laborious. Herein, we present a rapid and scalable route to chiral bromolactones as enabling precursors in the synthesis of sesquiterpene lactones.